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Pharmacogenetics aspects of oral anticoagulants therapy

Rationale: Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or...

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Autores principales: Militaru, FC, Vesa, SC, Pop, TR, Buzoianu, AD
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Carol Davila University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392103/
https://www.ncbi.nlm.nih.gov/pubmed/25866574
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author Militaru, FC
Vesa, SC
Pop, TR
Buzoianu, AD
author_facet Militaru, FC
Vesa, SC
Pop, TR
Buzoianu, AD
author_sort Militaru, FC
collection PubMed
description Rationale: Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or intra-individual variability in response to the treatment. Objective: to establish the influence of several genetic factors on VKA efficacy and adverse reactions. Methods and Results: The metabolism of VKA differs depending on their chemical structure: indandiones derivatives (fluindione) or coumarin derivatives (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants being associated with differences in the enzymatic activity of CYP2C9. The most important in terms of their frequency in the general population are CYP2C9*2 and CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK metabolism. Various polymorphisms in the VKORC1 gene have been described. VKORC1*2 haplotype seems to be the most important in relation to the variability in response to VKA. Discussions: Various studies have shown a relationship between the genotype and the mean warfarin maintenance dosing: in patients carrying 2C9*1/ *2 alleles, the dose is reduced by 18-40% in patients carrying 2C9*2/ *2 alleles, by 21-49% in patients carrying 2C9*1/ *3 alleles. The A allele of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for a lower dose of acenocoumarol in patients on anticoagulant therapy. Abbreviations: SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists, C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International Normalized Ratio
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spelling pubmed-43921032015-06-01 Pharmacogenetics aspects of oral anticoagulants therapy Militaru, FC Vesa, SC Pop, TR Buzoianu, AD J Med Life General Articles Rationale: Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or intra-individual variability in response to the treatment. Objective: to establish the influence of several genetic factors on VKA efficacy and adverse reactions. Methods and Results: The metabolism of VKA differs depending on their chemical structure: indandiones derivatives (fluindione) or coumarin derivatives (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants being associated with differences in the enzymatic activity of CYP2C9. The most important in terms of their frequency in the general population are CYP2C9*2 and CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK metabolism. Various polymorphisms in the VKORC1 gene have been described. VKORC1*2 haplotype seems to be the most important in relation to the variability in response to VKA. Discussions: Various studies have shown a relationship between the genotype and the mean warfarin maintenance dosing: in patients carrying 2C9*1/ *2 alleles, the dose is reduced by 18-40% in patients carrying 2C9*2/ *2 alleles, by 21-49% in patients carrying 2C9*1/ *3 alleles. The A allele of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for a lower dose of acenocoumarol in patients on anticoagulant therapy. Abbreviations: SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists, C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International Normalized Ratio Carol Davila University Press 2015 /pmc/articles/PMC4392103/ /pubmed/25866574 Text en ©Carol Davila University Press http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle General Articles
Militaru, FC
Vesa, SC
Pop, TR
Buzoianu, AD
Pharmacogenetics aspects of oral anticoagulants therapy
title Pharmacogenetics aspects of oral anticoagulants therapy
title_full Pharmacogenetics aspects of oral anticoagulants therapy
title_fullStr Pharmacogenetics aspects of oral anticoagulants therapy
title_full_unstemmed Pharmacogenetics aspects of oral anticoagulants therapy
title_short Pharmacogenetics aspects of oral anticoagulants therapy
title_sort pharmacogenetics aspects of oral anticoagulants therapy
topic General Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392103/
https://www.ncbi.nlm.nih.gov/pubmed/25866574
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